IL-4/IL-13 Heteroreceptor Influences Th17 Cell Conversion and Sensitivity to Regulatory T Cell Suppression To Restrain Experimental Allergic Encephalomyelitis.
IL-4/IL-13 Heteroreceptor Influences Th17 Cell Conversion and Sensitivity to Regulatory T Cell Suppression To Restrain Experimental Allergic Encephalomyelitis.
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DOI：
10.4049/jimmunol.1700372
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发表时间：
2017-10-01
期刊：
影响因子：
--
通讯作者：
Zaghouani H
中科院分区：
文献类型：
--
作者：
Barik S;Ellis JS;Cascio JA;Miller MM;Ukah TK;Cattin-Roy AN;Zaghouani H
IL-4和IL-13被定义为抗炎细胞因子，可以对抗髓鞘反应性T细胞，调节实验性变态反应性脑脊髓炎(EAE)。然而，目前尚不清楚内源性IL-4和IL-13是否参与外周耐受的维持，以及它们的功能是否与T调节细胞(Tregs)相协调。在这里，我们利用IL-4和IL-13的共同细胞因子受体，即IL-4Rα/IL-13R Th1异源受体(HR)受损的小鼠，并确定内源性IL-4和IL-13通过HR缺乏信号是否以Treg依赖的方式影响效应α和Th17细胞的功能。结果表明，HR(13R-/-)缺乏的小鼠比HR(13R+/+)充足的小鼠更容易患上EAE，并且发病早，病情更严重。此外，与来自13R+/+小鼠的Th17效应器相比，来自13R-/-小鼠的Th17细胞转化为Th1细胞的能力降低，并且对Tregs抑制的敏感性降低。这些观察表明，IL-4和IL-13可能通过HR发挥作用，影响Th17细胞转化为Th1细胞，并获得对抑制的敏感性增加，从而控制免疫介导的中枢神经系统炎症。这些以前未被承认的发现揭示了细胞因子对外周耐受和自身免疫控制的贡献的错综复杂的基础。
IL-4 and IL-13 have been defined as anti-inflammatory cytokines which can counter myelin-reactive T cells and modulate experimental allergic encephalomyelitis (EAE). However, it is not known whether endogenous IL-4 and IL-13 contribute to the maintenance of peripheral tolerance and whether their function is coordinated with T regulatory cells (Tregs). Here, we utilized mice in which the common cytokine receptor for IL-4 and IL-13, namely the IL-4Rα/IL-13Rα1 heteroreceptor (HR), is compromised and determined whether the lack of signaling by endogenous IL-4 and IL-13 through the HR influences the function of effector Th1 and Th17 cells in a Treg-dependent fashion. The findings indicate that mice-deficient for the HR (13R-/-) are more susceptible to EAE than mice sufficient for the HR (13R+/+) and develop early onset and more severe disease. Moreover, Th17 cells from 13R-/- mice had reduced ability to convert to Th1 cells and displayed reduced sensitivity to suppression by Tregs relative to Th17 effectors from 13R+/+ mice. These observations suggest that IL-4 and IL-13 likely operate through the HR and influence Th17 cells to convert to Th1 cells and to acquire increased sensitivity to suppression leading to control of immune-mediated central nervous system inflammation. These previously unrecognized findings shed light on the intricacies underlying the contribution of cytokines to peripheral tolerance and control of autoimmunity.
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DOI：
10.1084/jem.20041538
发表时间：
2005-01-17
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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DOI：
10.4049/jimmunol.1203552
发表时间：
2013-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cascio JA;Haymaker CL;Divekar RD;Zaghouani S;Khairallah MT;Wan X;Rowland LM;Dhakal M;Chen W;Zaghouani H
通讯作者：
Zaghouani H